Utilidad de la resonancia magnética en el diagnóstico de las enfermedades musculares hereditarias / Utility of magnetic resonance imaging in the diagnosis of hereditary muscular diseases

Hereditary muscular diseases are rare disorders, due to a genetic defect that causes an alteration in the structure or function of the muscle fibers. They may present at any stage of life and their definitive diagnosis usually requires muscle biopsy. While the most frequent hereditary myopathies have a relatively characteristic clinical presentation, there is a substantial part thereof in which the symptoms are non-specific and the definitive diagnosis may take a long time. Magnetic Resonance Imaging (MRI) has earned a place in the diagnostic process of this last group of myopathies, confirming the presence of muscle involvement and raising diagnostic approaches based on its distribution, information that guides the immunohistochemical and/or genetic study necessary for the definitive diagnosis. In this article we review the basic study protocols with MRI of the myopathies and their interpretation, also showing some cases of these diseases.

Las enfermedades musculares hereditarias son patologías raras, debidas a un defecto genético que causa una alteración en la estructura o funcionamiento de las fibras musculares. Pueden debutar en cualquier etapa de la vida y su diagnóstico definitivo suele requerir de biopsia muscular. Si bien las miopatías hereditarias más frecuentes tienen una presentación clínica relativamente característica, existe una parte importante de ellas en que los síntomas son poco específicos y su diagnóstico definitivo puede tomar largo tiempo. La Resonancia Magnética (RM) ha ganado un espacio en el proceso diagnóstico de este último grupo de miopatías, confirmando la presencia del compromiso muscular y planteando aproximaciones diagnósticas en base a su distribución, información que acota el estudio inmunohistoquímico y/o genético necesario para el diagnóstico definitivo.En el presente artículo revisaremos los protocolos de estudio básico con RM de las miopatías y su interpretación, mostrando también algunos casos de estas enfermedades.

Sueño en el niño / Sleep in children

Los trastornos del sueño en los niños son frecuentes, pueden afectar la conducta, aprendizaje, crecimiento del niño, ser causa de stress familiar y, si no se tratan, pueden persistir por largos periodos. Los problemas del sueño los podemos agrupar en tres categorías principales: falta de sueño (insomnio), exceso de sueño (hipersomnia) y alteración de la conducta durante el sueño (parasomnias). Las causas son múltiples pero la mayoría se debe a expectativas inapropiadas por parte de los padres, por falta de conocimiento y/o una mala higiene del sueño. El sueño, al igual que el comer, se aprende. El niño se adapta a su medio y éste, le crea el hábito. Luego, el tratamiento de los problemas de sueño en los niños comienza por la educación de los padres para que establezcan una buena higiene del sueño desde las etapas tempranas de la vida.

Sleep disorders in children are common they can harm a child's learning abilíty, its behaviour and even its physical development. They can be a cause of family stress and, if not treated, can persist for long periods of time. Sleepproblems can be grouped into three main categories: sleeplessness (insomnia), excessive sleepiness (hypersomnia) and episodic disturbance of sleep behaviour (parasomnias). The underlying causes are variable but are mainly due to inappropriate parental expectations due to their lack of information andlor to bad sleep hygiene. Sleeping, like eating, can be learned. Children will adapt to their environment and this, in turn, creates their habits. Thus, the treatment of sleep disorders in children starts by teaching the parents how to establísh a good sleep hygiene beginning at an early stage of the child's life.

Avances en el diagnóstico y manejo de las enfermedades neuromusculares / Advances in the diagnosis and management of neuromuscular diseases

Las enfermedades neuromusculares (ENM) hereditarias son un conjunto de diversas patologías que debido a la identificación de nuevas proteínas y genes implicados en su etiopatogenia, constituyen entidades clínicas en constante evolución y expansión. Estos avances han permitido comprender mejor los mecanismos patológicos y han impulsado el desarrollo de nuevas técnicas diagnósticas y numerosas investigaciones centradas en tratamientos más específicos. Los clásicos límites entre unas y otras afecciones se han transformado en fronteras menos nítidas, al conocer que diversas manifestaciones fenotípicas pueden corresponder a la alteración de un mismo gen y a la inversa que un mismo síndrome puede ser originado por la alteración de diferentes genes. Este artículo describe las principales proteínas y genes relacionados con las ENM, su clasificación y los avances en el diagnóstico y tratamiento de algunas de las más representativas: la distrofia muscular de Duchenne, la atrofia muscular espinal y las laminopatías.

Extraordinary breakthroughs in the molecular pathogenesis of inherited neuromuscular diseases have resulted evolving genetic classification of neuromuscular disorders and the development of new diagnostic tools. This remarkable progress has introduced new genetic tests and has raised the real possibility of new and more specific therapeutics strategies for these conditions. This review focus on the different groups of proteins currently recognized as being involved in myopathies and muscular dystrophies and discuss some clinical and therapeutical aspect of the Duchenne muscular dystrophy, spinal muscular dystrophy and laminopathies as representatives models.

[Aripiprazole for the treatment of Tourette syndrome. Experience in 10 patients]. / Aripiprazole en el tratamiento sintomático del síndrome de Gilíes de la Tourette (enfermedad de los tics).

BACKGROUND: Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, attentional deficit, poor control of impulses and obsessive compulsive disorder. Pharmacological treatment is often disappointing due to partial response and frequent poor tolerance to neuroleptic drugs which are otherwise the most effective therapy so far. AIM: To report a lasting improvement obtained with a new drug, aripiprazole that acts modulating both dopaminergic and serotoninergic neurotransmission. MATERIAL AND METHODS: Ten patients refractory to their usual therapy, aged 10 to 35 years, were switched to aripiprazole in an open trial. RESULTS: Nine of the 10 patients showed a significant response assessed by the Yale severity tics rating scale and the clinical global impression scale (p <0.01). No relevant adverse effects were observed. CONCLUSIONS: Aripiprazole may be a good pharmacological option for patients with Tourette syndrome.

Aripiprazole en el tratamiento sintomático del síndrome de Gilíes de la Tourette (enfermedad de los tics) / Aripiprazole for the treatment of Tourette syndrome. Experience in 10 patients

Background: Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, attentional deficit, poor control of impulses and obsessive compulsive disorder. Pharmacological treatment is often disappointing due to partial response and frequent poor tolerance to neuroleptic drugs which are otherwise the most effective therapy so far. Aim: To report a lasting improvement obtained with a new drug, aripiprazole that acts modulating both dopaminergic and serotoninergic neurotransmission. Material and methods: Ten patients refractory to their usual therapy, aged 10 to 35 years, were switched to aripiprazole in an open trial. Results: Nine of the 10 patients showed a significant response assessed by the Yale severity tics rating scale and the clinical global impression scale (p <0.01). No relevant adverse effects were observed. Conclusions: Aripiprazole may be a good pharmacological option for patients with Tourette syndrome.

Síndrome de McLeod: compromiso multisistémico asociado a neuroacantocitosis ligada al cromosoma X, en una familia chilena / McLeod syndrome: Multisystem involvement associated with neuroacanthocytosis linked to X chromosome. Report of two related cases

Neurological abnormalities associated with spiculated, "acanthocytic" red cells in blood have been described as neuroacanthocytosis. This is a heterogeneous group of conditions that can be clearly subdivided on the basis of recent genetic findings. The McLeod Syndrome, one of the core neuroacanthocytosis syndromes, is a rare X-linked disorder caused by mutations of the XK gene, an X-chromosomal gene of unknown function characterized by haemopoietic abnormalities and late-onset neurological and muscular defects. We report two Chilean brothers with the McLeod phenotype who showed important psychiatric features. The diagnosis may be elusive if the presence of acanthocytosis is not properly studied. We describe a method which allowed the diagnosis that unmasked acanthocytosis. Otherwise the condition could have remained undiagnosed as it had been for decades in this family. This syndrome must be considered when assessing a familial movement disorder, specially affecting males with relevant psychiatric features. A reliable test for acanthocytosis assessment is available.

[McLeod syndrome: Multisystem involvement associated with neuroacanthocytosis linked to X chromosome. report of two related cases]. / Síndrome de McLeod: compromiso multisistémico asociado a neuroacantocitosis ligada al cromosoma X, en una familia chilena.

Neurological abnormalities associated with spiculated, "acanthocytic" red cells in blood have been described as neuroacanthocytosis. This is a heterogeneous group of conditions that can be clearly subdivided on the basis of recent genetic findings. The McLeod Syndrome, one of the core neuroacanthocytosis syndromes, is a rare X-linked disorder caused by mutations of the XK gene, an X-chromosomal gene of unknown function characterized by haemopoietic abnormalities and late-onset neurological and muscular defects. We report two Chilean brothers with the McLeod phenotype who showed important psychiatric features. The diagnosis may be elusive if the presence of acanthocytosis is not properly studied. We describe a method which allowed the diagnosis that unmasked acanthocytosis. Otherwise the condition could have remained undiagnosed as it had been for decades in this family. This syndrome must be considered when assessing a familial movement disorder, specially affecting males with relevant psychiatric features. A reliable test for acanthocytosis assessment is available.

[The problem of hepatitis C virus infection in blood donors. Clinico-epidemiological, virological and histological evaluation]. / Problemática de la infección por el virus de la hepatitis C en donantes de sangre. Evaluación Clínico-epidemiologica, virologica e hestologica.

Our aim was to identify prospectively, with a case-control survey, risk factors for hepatitis C virus (HCV) infection in volunteer blood donors and to assess the histological features and their correlation with transaminase (ALT) level and viremia. In a Liver Unit of a referral-based University Hospital, 248 blood donors were evaluated for risk factors, according to definitive ELISA test and 132 were considered true positive. Of these, 132 anti-HCV(+) blood donors were age and sex-matched with the anti-HCV-negative group (n = 116). There was a high frequency in the anti-HCV(+) group of intravenous drug abuse (IVDA) (22%), history of major surgery (20.4%), tattooing (12.1%), non IVDA (17.4%), and multiple sexual partners or history of sexual transmitted diseases (25.7%). At least one risk factor was identified in 76.52% of the antiHCV(+) donors vs 34.4% in the anti-HCV (-) group (p = 0.000). A total of 71 patients accepted a liver biopsy; chronic liver disease was present in 85.9% (n = 61) (mean Knodell score 6.75). ALT was elevated in 69% (n = 49) and HCV RNA was detectable in 76% of patients. It can be concluded that in our study 76.5% of anti HCV positive blood donors showed at least one risk factor for HCV infection detected by a second highly efficient interview. Twenty two percent admitted to prior intravenous drug use although this disqualifies them for blood donation, but was not identified by the screening process. Most blood donors with anti HCV(+) had chronic hepatitis C regardless of their serum ALT levels. Normal ALT did not exclude liver disease.

Detection of heterozygosity loss in microdissected fine needle aspiration specimens of breast carcinoma.

OBJECTIVE: To use the polymerase chain reaction (PCR) to detect loss of heterozygosity (LOH) in microdissected cells form cytologic smears obtained by fine needle aspiration (FNA) from 20 cases of invasive breast carcinoma. STUDY DESIGN: In each case, histologic sections of the primary tumor were also available. Tumor and nontumor cells were dissected from both the cytologic smear and tissue section in all cases except in three smears that showed only tumor cells. RESULTS: LOH was identified in 10 of 19 informative cases using two polymorphic DNA markers at chromosome 11q13 (INT-2, PYGM). The same results were obtained in both the cytologic and histologic specimens, including three cases that had hypocellular cytologic smears. CONCLUSION: FNA of breast lesions provides adequate samples for direct microdissection of the cytologic smear to detect LOH using PCR amplification.

[Immunohistochemical analysis of p53 and c-erbB-2 in breast cancer]. / Análisis inmunohistoquímico de p53 y c-cerbB-2 en el carcinoma de mama.

We have studied by immunohistochemistry the nuclear expression of p53 and the finding of oncoprotein c-erbB-2 in a series of 85 breast carcinomas. The tissue was fixed in buffered formalin and embedded in paraffin. The primary antisera were obtained from Biogenex (USA), Bp53-12, monoclonal, used in a dilution of 1:100 for p53 and from Triton Diagnostics (USA), pAB-1, polyclonal, used in a dilution of 1:200 for c-erbB2. The detection system was the Vectastain Elite kit obtained from Vector Laboratories (USA). The results were compared with several morphological features of the tumors such as size and type of the tumor, extension of the intraductal component, nuclear grade, axillary lymph node metastasis and estrogen receptor data as well as with total and disease free survival. The oncoprotein p53 was detected in the nuclei in 25 (29.4%) of our cases (Fig 1). Its presence was correlated with tumor size (p < 0.01), high nuclear grade (p < 0.0001) and estrogen receptor negative tumors (p < 0.0001). There was an inverse relationship between p53 expression and 5 year disease free survival (p < 0.005). In 21 (24.7%) of the cases we found amplification of c-erbB-2. The staining pattern was membranous (Fig. 2). It was correlated significantly with the ductal type of invasive carcinoma (p < 0.05), an associated extensive intraductal component (p < 0.001), estrogen receptor negative tumors (p < 0.0001) and shortening of disease free survival in the patients with positive axillary lymph nodes (p < 0.005). In 9 cases we found staining for both markers without statistically significant relationship with the other features studied. We conclude that the presence of these genetic alterations demonstrated by immunohistochemistry were, in our series, unfavourable prognostic factors in invasive breast cancer.

Análisis inmunohistoquímico de p53 y c-cerbB-2 en el carcinoma de mama. / [Immunohistochemical analysis of p53 and c-erbB-2 in breast cancer]

We have studied by immunohistochemistry the nuclear expression of p53 and the finding of oncoprotein c-erbB-2 in a series of 85 breast carcinomas. The tissue was fixed in buffered formalin and embedded in paraffin. The primary antisera were obtained from Biogenex (USA), Bp53-12, monoclonal, used in a dilution of 1:100 for p53 and from Triton Diagnostics (USA), pAB-1, polyclonal, used in a dilution of 1:200 for c-erbB2. The detection system was the Vectastain Elite kit obtained from Vector Laboratories (USA). The results were compared with several morphological features of the tumors such as size and type of the tumor, extension of the intraductal component, nuclear grade, axillary lymph node metastasis and estrogen receptor data as well as with total and disease free survival. The oncoprotein p53 was detected in the nuclei in 25 (29.4

) of our cases (Fig 1). Its presence was correlated with tumor size (p < 0.01), high nuclear grade (p < 0.0001) and estrogen receptor negative tumors (p < 0.0001). There was an inverse relationship between p53 expression and 5 year disease free survival (p < 0.005). In 21 (24.7

) of the cases we found amplification of c-erbB-2. The staining pattern was membranous (Fig. 2). It was correlated significantly with the ductal type of invasive carcinoma (p < 0.05), an associated extensive intraductal component (p < 0.001), estrogen receptor negative tumors (p < 0.0001) and shortening of disease free survival in the patients with positive axillary lymph nodes (p < 0.005). In 9 cases we found staining for both markers without statistically significant relationship with the other features studied. We conclude that the presence of these genetic alterations demonstrated by immunohistochemistry were, in our series, unfavourable prognostic factors in invasive breast cancer.

Immunohistochemical analysis of cathepsins D, B, and L in human breast cancer.

Cathepsins D, B, and L are acidic lysosomal proteinases involved in intracellular protein turnover. Increased levels of these enzymes have been reported to be indicators of aggressive tumor behavior in human and rodent tumors. In breast cancer increased levels of cathepsin D have been reported to be an independent prognostic factor in women with stage I disease. We used standard immunohistochemical techniques on formalin-fixed, paraffin-embedded tissue to examine the levels of cathepsins D, B, and L in 80 carcinomas of the breast and compared that with other indicators of aggressive tumor behavior, including stage of disease, tumor size, nuclear grade, estrogen receptor status, disease recurrence, and 5-year survival rates. Positive granular cytoplasmic staining was detected for cathepsin D in 90% of the tumors, for cathepsin B in two thirds of the tumors, and for cathepsin L in approximately one half of the tumors. Positive staining also was seen in normal breast epithelium, areas of apocrine metaplasia, stromal fibroblasts, and macrophages. Our results did not show a correlation between the expression of cathepsins D, B, and L and other indicators of aggressive tumor behavior. We conclude that the results obtained using polyclonal anticathepsin antibodies do not support the prognostic usefulness of immunohistochemical analysis of these three proteinases in tumor cells in human breast cancer.